Partial and total monosomal karyotypes in myelodysplastic syndromes: Comparative prognostic relevance among 421 patients

Abstract

Myelodysplastic syndromes (MDS) include a group of heterogeneous hematological disorders with a variable risk of leukemic evolution and short survival. Around 40-50% of patients show abnormal karyotypes that are mostly characterized by monosomies or deletions. Cytogenetic findings are an independent prognostic factor and the International prognostic scoring system (IPSS) differentiates three cytogenetic categories, despite the Intermediate one being heterogeneous. The aim of this study, including 421 Argentinean patients with primary MDS, is to characterize the cytogenetic profile, to test its prognostic value and to compare partial and monosomal karyotypes against other cytogenetic findings. An abnormal karyotype (median survival: 26 months) was observed in 176 patients. The presence of complex karyotypes, number of alterations, and the IPSS cytogenetic groups showed significant differences for predicting outcome. Behavior of patients with isolated deletions (median survival: 49 months) did not differ from those with normal karyotype (56 months, P 5 0.654) or Good prognostic findings (43 months, P 5 0.371). However, a worse prognosis was observed when another alteration was added (31 months, P 5 0.043). Karyotypes with autosomal monosomies (median survival: 16 months) had a prognostic impact similar to other Poor cytogenetic findings (17 months, P 5 0.626). In our population classified according to French-American-British (FAB) or World Health Organization (WHO), this new categorization of cytogenetic abnormalities, recognizing three different risk groups, showed an independent prognostic impact and a better discriminating power than the IPSS categories. It can be concluded that all isolate deletions (excluding 7q-) are good prognostic findings and all monosomies (excluding Y chromosome loss) are bad indicators. Am. J. Hematol. 86:540-545, 2011. V

IPSS‐R in 555 Taiwanese patients with primary MDS: Integration of monosomal karyotype can better risk‐stratify the patients

“…Similarly, Gangat et al [17] could not find the prognostic superiority of IPSS-R very good karyotype in a study of 783 patients with primary MDS and the prognosis among very good, intermediate, and poor cytogenetic categories seemed not different. In addition to AML [16], presence of MK was recently found to be a poor prognostic factor in MDS [18,19]. Patnaik et al [18] showed that MK could further identify a prognostically worse group in 127 patients with complex karyotype and Gangat et al [17] demonstrated MK adversely affected survival in both poor and very poor karyotype groups.…”

Validation of the new comprehensive cytogenetic scoring system (NCCSS) on 630 consecutive de novo MDS patients from a single institution

“…Despite the efforts of many researchers [6][7][8][9][10][11][12][13]16,20], the prognostic significance of rare single chromosomal defects, double defects and unrelated clones, which flag the extreme heterogeneity of the MDS cytogenetic pattern [2,21,[28][29][30][31]41], has remained ill defined. In fact, most of the aforementioned studies provided conflicting results due to the small number of patients studied.…”

“…The International Prognostic Scoring System (IPSS) [8] was that most commonly used and has been now revised [17][18][19]. Thus, cytogenetic abnormalities remain one of the major determinants of MDS pathogenesis, diagnosis, prognosis and guide any potential treatment decisions [12][13][14][15][16][17][18][19][20][21][22][23][24][25], however more sensitive techniques such as array Comparative Genomic Hybridization, Single Nucleotide Polymorphism arrays (SNP-a) and Next-Generation Sequencing are still used in the research setting only [26][27][28][29][30][31]. The IPSS precisely defines the prognostic value of the most frequent chromosomal defects, whereas it does not define rare or combined abnormalities, which are included within the intermediate category [8].…”

“…In the last 10 years, large patient series have provided some relevant information on rare isolated abnormalities [9][10][11][12][13], but very few have provided information on combined defects [10,13]. In addition, it has become evident that the clinical outcome of patients with a complex karyotype, previously defined by the presence of 3 defects, worsens with an increase in the number of chromosomal defects [13,20,21]. These limitations have spurred the revision of the IPSS cytogenetic categories and have led to the development of the NCCSS [17][18][19].…”

Myelodysplastic syndromes in South America: A multinational study of 1080 patients

“…There are few others direct comparisons of MDS patients from other countries and little is known about South-American (SA) patients. There are previous reports that validate prognostic scoring systems in Argentinean population [17][18][19], and attempts for epidemiological description in Brazilian reduced series [ [20], Velloso et al, 2007, personal communication], but epidemiological data in Chile are not available yet. Our aim was to describe clinical characteristics of SA MDS population, to compare our series with diverse ethnicity, and to evaluate prognostic factors and scoring systems.…”